PMID: 

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2019 Dec 25 ;48(6):617-624. PMID: 31955535

Abstract Title: 

[Effects of resveratrol on aging of mesenchymal stem cells and its mechanism].

Abstract: 

OBJECTIVE: To investigate the effects of resveratrol (Res) on aging of marrow mesenchymal stem cells (MSCs), and to explore its mechanism.METHODS: MSCs were isolated from young SD rats and cultured. The optimal D-gal concentration for induction of MSCs senescence was determined. Then MSCs were randomly divided into four groups, namely the control group, 10μmol/L, 50μmol/L and 100μmol/L Res groups. After the cells were treated with different concentration of Res for 48 h, the senescence-associated changes were examined with senescence-associated-β-galactosidase (SA-β-gal) staining; the expression of p53, p16 and γ-H2AX was evaluated by Western blot. The total active oxygen species (ROS) level was determined by flow cytometry with DCFH-DA staining. In order to assess the effect of Res on the mitochondrial function, MitoSox Red staining was used to detect mitochondrial ROS levels in each group, mitochondrial membrane potential was detected by JC-1 assay, mPTP method was used to detect mitochondrial membrane channel opening level, and Western blot was used to detect the expression level of cytoplasmic cytochrome C (Cyt-C).RESULTS: D-gal 10 and 50 g/L significantly increased the number of SA-β-gal positive cells and the level of mitochondrial ROS (all

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PMID: 

Adv Pharm Bull. 2020 Jan ;10(1):88-96. Epub 2019 Dec 11. PMID: 32002366

Abstract Title: 

Resveratrol Effect on Adipose-Derived Stem Cells Differentiation to Chondrocyte in Three-Dimensional Culture.

Abstract: 

Adipose stem cells (ASCs) are pluripotent cells with the ability of self-renewal and differentiation into different types of mesenchymal cells. As cartilage repair is difficult due to lack of blood capillary, resveratrol (Res) is a polyphenolic compound with diverse biological properties to be possibly used in this case. The aim of the present study was to investigate the effect of Res on differentiation of ASCs into chondrocyte in a three-dimensional (3D) culture model.Subcutaneous adipose tissues were prepared and digested enzymatically, and passed through cell strainer. ASCs were harvested in the fourth passage, and divided into five groups. The control group received chondrogenic differentiation medium (CDM) while the experimental groups received CDM plus different doses of Res (1, 10, 20, and 50µM) for 21 days. Expression of cartilage specific genes and Sirtuin1 (SIRT 1), cell viability, apoptosis and ferric reducing antioxidant power (FRAP) were detected using reverse transcription polymerase chain reaction (RT-PCR), MTT assay, TUNEL and acridine orange/ethidium bromide (AO/EB) staining.One-way ANOVA and non-parametric Mann-Whitney U test were used for data analyses.ASCs were differentiated to chondrocyte by CDM in a three-dimensional culture. 10 and 20µM doses of Res showed the most proliferating effect on ADSCs. The SIRT 1 genes expression and FRAP level also increased significantly compared to the control group (

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Chem Biol Interact. 2019 Feb 1 ;299:131-139. Epub 2018 Dec 11. PMID: 30543783

Abstract Title: 

Methyl ferulic acid attenuates liver fibrosis and hepatic stellate cell activation through the TGF-β1/Smad and NOX4/ROS pathways.

Abstract: 

Liver fibrosis is a pathological wound-healing response caused by chronic liver damage due to a virus, autoimmune disorder, or drugs. Hepatic stellate cells (HSCs) play an essential role in the pathogenesis of liver fibrosis. Methyl ferulic acid (MFA), a biologically active monomer, has a protective effect on liver injury. However, the effects and roles of MFA in liver fibrosis remain unknown. The purpose of the current study was to investigate the effect of MFA on hepatic fibrosis and the underlying mechanisms. Human hepatic stellate LX-2 cells were exposed to 5 μg/L TGF-β1 for 48 h to stimulate liver fibrosis in vitro. Using MTT, RT-PCR and Western blot analysis, we revealed that MFA significantly inhibited the proliferation of LX-2 cells as well as decreased the expressions of α-SMA and type I collagen in LX-2 cells.SD rats were fed with ethanol, and this combined with the intraperitoneal injection of CClinduced liver fibrosis in vivo. We found that the administration of MFA markedly decreased the levels of hyaluronic acid (HA), procollagen type III (PC-III), type IV collagen (CIV) and laminin (LN) in the serum, inhibited the expression ofα-smooth muscle actin (α-SMA) as well as type I and type III collagen, and up-regulated the ratio of MMP-2/TIMP-1 in rats. The antifibrotic effects of MFA were also evaluated by H&E staining and Masson's trichrome staining. In addition, further studies suggested that this protection by MFA from liver fibrosis was possibly related to the inhibition of TGF-β1/Smad and NOX4/ROS signalling. In conclusion, our results demonstrate that MFA attenuated liver fibrosis and hepatic stellate cell activation by inhibiting the TGF-β1/Smad and NOX4/ROS signalling pathways.

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PMID: 

Saudi J Biol Sci. 2019 Jan ;26(1):201-209. Epub 2017 Sep 21. PMID: 30622427

Abstract Title: 

Influence of resveratrol on liver fibrosis induced by dimethylnitrosamine in male rats.

Abstract: 

Liver fibrosis is a significant health problem which represents the liver's scarring process and response to injury through deposition of collagen and extracellular matrix, and ultimately leads to cirrhosis. Resveratrol is a naturally occurring phytoalexin found predominantly in grapes. This study aimed to investigate the antifibrotic role of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were divided into four groups and treated for three weeks; control, resveratrol administered orally (20 mg/kg daily), DMN intraperitoneally injected (10 mg/kg 3 days/week), and the last group was pre-treated daily with resveratrol then injected with DMN, 3 days/week. DMN administration induced severe liver pathological alterations. However, oral administration of resveratrol before DMN significantly prevented the induced loss in body weight, as well as the increase in liver weight which arise from DMN administration. Resveratrol has also inhibited the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin levels. Furthermore, resveratrol significantly increased hepatic reduced glutathione (GSH) levels and reduced the levels of malondialdehyde (MDA) due to its antioxidants effect as well as increased serum protein levels. In addition, DMN induced elevation in hydroxyproline content. On the other hand, hydroxyprolinelevel was significantly reduced in the resveratrol pretreated rats. Resveratrol has also remarkably maintained the normal liver lobular architecture. Moreover, resveratrol had displayed potent potentials to prevent collagen deposition, lymphocytic infiltration, necrosis, steatosis, vascular damage,blood hypertention, cholangiocyte proliferation. It can be concluded that resveratrol has a marked protective role on DMN-induced liver fibrosis in rats, and can be considered as antiproliferative, antihypertensive, as well as antifibrotic agent and may be used to block the development of liver fibrosis.

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PMID: 

Cell Tissue Res. 2018 Oct ;374(1):111-120. Epub 2018 Jun 27. PMID: 29951700

Abstract Title: 

Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress.

Abstract: 

Survival of mesenchymal stem cells (MSCs) against oxidative stress and inflammation is vital for effective stem cell therapy. The reactive oxygen species (ROS) result in apoptosis and release of inflammatory mediators. Adipose-derived stem cells (ASCs) have shown promise for stem cell therapy owing to their anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits of vitamin E against hydrogen peroxide (HO)-induced oxidative stress in rat bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against HO-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500 μM HOwith or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGEproduction and caspase-3 activity were observed after vitamin E treatment. Gene expression analysis of vitamin E-treated pASCs showed down-regulated expression for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3, p53, BAX, MDM2, NFκB, HIF1α and VEGF-A genes. On the other hand, expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2, BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following vitamin E treatment. The findings of this study may help in developing effective stem cell therapy for the diseases characterized by the oxidative stress and inflammation.

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PMID: 

Molecules. 2018 Dec 6 ;23(12). Epub 2018 Dec 6. PMID: 30563251

Abstract Title: 

(-)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Abstract: 

Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization ofhuman BMSCs (hBMSCs).

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PMID: 

Biochem Biophys Rep. 2019 Dec ;20:100678. Epub 2019 Aug 16. PMID: 31467991

Abstract Title: 

Antifibrotic effect of methylated quercetin derivatives on TGFβ-induced hepatic stellate cells.

Abstract: 

Quercetin (QCT) and isorhamnetin (ISO), natural flavonoids, were both shown to possess antifibrotic activity inandmodels of hepatic fibrosis. Although ISO is a direct metabolite of QCT differing by a methyl group, it has been reported to be absorbed more adequately and eliminated slower than QCT after oral administration. Our aim of the study was to investigate biological effect of mono-methylated QCT derivatives against fibrosis using rat hepatic stellate cells (HSC-T6). All test derivatives were synthesized from QCT. HSC-T6 cells were induced by TGFβ and treated with derivatives followed by cell proliferation assay, immunofluorescence staining of αSMA, and gene expression analysis of fibrosis markers. All compounds showed a dose- and time-dependent antiproliferation effect. ISO, 3-O-methylquercetin (3MQ), and rhamnetin (RHA) reduced αSMA mRNA; 3MQ prevented the augmentation of collagen I mRNA; and compounds, except azaleatin and 3MQ, reduced Timp1 mRNA expression in TGFβ-induced HSCs. In conclusion, each compound had singular effect against different features of fibrosis depending on the position of methyl group although the furthermechanism of action of compounds during fibrosis development remains to be investigated. These findings suggest that antifibrotic effect of quercetin can be enhanced by adding methyl group on functionally important position.

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PMID: 

Clin Respir J. 2018 Jul ;12(7):2220-2227. Epub 2018 Apr 16. PMID: 29570946

Abstract Title: 

Serum 25-hydroxyvitamin D levels in hospitalized adults with community-acquired pneumonia.

Abstract: 

INTRODUCTION: Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Several studies have shown an association between vitamin D deficiency and increases susceptibility to respiratory tract infections.OBJECTIVE: The aim of this study was to evaluate the serum 25-hydroxyvitamin D (25OHD) levels in hospitalized adults in general room with CAP.MATERIALS AND METHODS: An observational study was carried out in 207 hospitalized adults of both sex with CAP (>18 years) from Rosario city, Argentina (32° 52' 18″S) between July 2015 and June 2016.RESULTS: In total, 167 patients were included in the data analysis [59% women (57.4 ± 19.6 years), body mass index 27.2 ± 7.8 kg/m]. In brief, 63% showed unilobar infiltrate and 37% were multilobar. The CURB-65 index was 66.5% low risk, 16.0% intermediate risk and 17.5% high risk. According to Charlson comorbidity index (CCI) 53.5% had not comorbidity (CCI = 0) and 46.5% showed CCI ≥ 1. The 25OHD level was: 11.92 ± 7.6 ng/mL (51.5%:30 ng/mL). Higher 25OHD were found in male (female: 10.8 ± 6.7 ng/mL, male: 13.5 ± 8.5 ng/mL, P = .02) and 25OHD correlated with age (r = -.17; P = .02). 25-Hydroxyvitamin D was also correlated with CURB65 index (r = -.13; P = .049), CCI (r = -.20, P = .007) and with the 10 years of life expectative (%) (r = .19;P = .008). In addition, higher 25OHD were found with lower CCI (CCI 0 = 13.0 ± 8.2 ng/mL, CCI ≥ 1= 10.5 ± 6.7 ng/mL; P = .0093).CONCLUSIONS: Hospitalized adults with CAP have lower 25OHD levels and would be associated with the severity of CAP.

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PMID: 

Korean J Intern Med. 2018 11 ;33(6):1129-1136. Epub 2018 Jun 20. PMID: 29914229

Abstract Title: 

Effect of vitamin D deficiency in Korean patients with acute respiratory distress syndrome.

Abstract: 

BACKGROUND/AIMS: Vitamin D modulates innate and adaptive immune responses, and vitamin D deficiency is associated with increased mortality in hospitalized patients with pneumonia. We evaluated the prevalence of vitamin D deficiency in Korean patients with acute respiratory distress syndrome (ARDS) and its effect on the clinical outcomes of ARDS.METHODS: We retrospectively analyzed the data of 108 patients who had a measured serum level of 25-hydroxy vitamin D3 (25(OH)D3) at the time of diagnosis with ARDS. The clinical outcomes were evaluated based on 25(OH)D3 levels of 20 ng/mL and stratified by quartiles of 25(OH)D3 levels.RESULTS: The mean age of patients was 59.4 years old; 77 (71.3%) were male. Vitamin D deficiency was found in 103 patients (95.4%). The mean 25(OH)D3 level was 8.3± 7.0 ng/mL. Neither in-hospital mortality (40.0% vs. 68.0%) nor 6-month mortality (40.0% vs. 71.8%) significantly differed between groups. There were no significant differences in 25(OH)D3 level between survivors (8.1 ± 7.6 ng/mL) and non-survivors (8.5 ± 6.8 ng/mL, p = 0.765). There were no trends toward a difference in mortality among quartiles of 25(OH)D3 levels. However, 25(OH)D3 levels were inversely related with length of hospital stay and intensive care unit stay among in-hospital survivors.CONCLUSION: Vitamin D deficiency was prevalent in Korean patients with ARDS. However, levels of vitamin D were not associated with mortality. A large, prospective study is needed to evaluate the effects of vitamin D deficiency on clinical outcomes of ARDS.

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PMID: 

Rep Biochem Mol Biol. 2019 Apr ;8(1):85-90. PMID: 31334293

Abstract Title: 

Association of Vitamin D Status with the Severity and Mortality of Community-Acquired Pneumonia in Iran during 2016-2017: A Prospective Cohort Study.

Abstract: 

Background: Community-acquired pneumonia (CAP) is a common disease considered as a major public health problem. It causes considerable morbidity and mortality despite antibiotic treatments. Hospital admission of CAP patients is a significant financial burden and many efforts are ongoing to decrease hospital stay durations. Vitamin D deficiency is associated with increased risk of respiratory infections. This study was designed to determine the association of vitamin D status with hospitalized CAP patient mortality and disease severity.Methods: This prospective cohort study examined 180 CAP patients admitted to a teaching Hospital in Tehran, Iran during 2016-2017. Their demographic and anthropometric characteristics were recorded. The disease severity was evaluated based on CURB-65. Vitamin D status was determined by measuring by serum 25-hydroxylated vitamin D (25(OH)D) with ELISA. The patients were followed for 30 days to evaluate their vitality.Results: One hundred and eighty pneumonia patients, including 104 males and 84 females, were recruited from respiratory disease, infectious disease, emergency, and ICU wards. Nearly 18% of the patients were current smokers. The CAP severity, evaluated by CURB-65, was determined to be non-severe in 74.4% of the patients. Patients were classified as vitamin D sufficient, insufficient, or deficient. Thirty percent of the patients were vitamin D sufficient, 18% were insufficient, and 52% were deficient. Thirty-day mortality was 40% (72 cases). Mortality was greater in males than in females (47.1% vs. 30.3%, p=0.03). The disease was significantly less severe in the patients who survived than in those who did not. The vitamin D status differed between males and females (p=0.027). The vitamin D status was lower in the more severe cases than in the less (p=0.036), and vitamin D deficiency was more prevalent in patients who died than in those who lived. Vitamin D concentration was negatively correlated with hospital stay duration. The 25(OH)D concentration was significantly greater in patients who survived than in those who did not (p

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